Re-endothelialization is delayed after drug-eluting stent (DES) implantation. In this setting, neointima is more prone to become lipid laden and develop neoatherosclerosis (NA), potentially increasing plaque vulnerability.

Optical coherence tomography and near-infrared spectroscopy with intravascular ultrasound were used to characterize NA in 65 (51 DES and 14 bare-metal stents) consecutive symptomatic patients with in-stent restenosis. Median duration poststent implantation was 33 months. Optical coherence tomography–verified NA was observed in 40 stents with in-stent restenosis (62%), was more prevalent in DES than bare-metal stents (68% versus 36%; P=0.02), and demonstrated significantly higher prevalence of thin-cap neoatheroma (47% versus 7%; P=0.01) in DES. Near-infrared spectroscopy assessment demonstrated that the total lipid core burden index (34 [interquartile range, 12–92] versus 9 [interquartile range, 0–32]; P<0.001) and the density of lipid core burden index (lipid core burden index/4 mm, 144 [interquartile range, 60–285] versus 26 [interquartile range, 0–86]; P<0.001) were higher in DES compared with bare-metal stents. Topographically, NA was classified as I (thin-cap NA), II (thick-cap NA), and III (peri-strut NA). Type I thin-cap neoatheroma was more common in DES (20% versus 3%; P=0.01) and in areas of the stented segment without significant in-stent restenosis (71%). Periprocedural myocardial infarction occurred only in DES (11 versus 0; P=0.05), of which 6 (55%) could be attributed to segments with >70% in-stent restenosis. By logistic regression, prior DES was the only independent predictor of both NA (odds ratio, 7.0; 95% confidence interval, 1.7–27; P=0.006) and periprocedural myocardial infarction (odds ratio, 1.8; 95% confidence interval, 1.1–2.4; P=0.05).

In-stent thin-cap neoatheroma is more prevalent, is distributed more diffusely across the stented segment, and is associated with increased periprocedural myocardial infarction in DES compared with bare-metal stents. These findings support NA as a mechanism for late DES failure.